Light controls cell behavior

ST. LOUIS – Light-sensitive proteins in cells can be coaxed to move toward a beam of light, a first step toward manipulating cells to control insulin secretion or heart rate using light, a new study out of Washington University School of Medicine has found.

“We have succeeded in using light as a kind of on-off switch to control cells’ behavior,” said principal investigator Dr. Narasimhan Gautam, a professor of anesthesiology at the university. “Much of the way cells behave is due to their ability to sense signals in the environment. In these experiments, what the cells sense is the presence of light.”

The researchers used genetic engineering techniques to introduce a light-sensing protein called an opsin – proteins made in the eye of humans and other animals, which translate light signals into vision – into immune cells. The proteins enabled the investigators to induce cell movement by shining a laser in the direction in which they wanted a cell to travel.

Scientists at Washington University School of Medicine in St. Louis used genetic engineering techniques to introduce light-sensitive proteins, called opsins, into immune cells. Here, an immune cell moves toward a light beam (blue box). The opsin in the cell (red) senses light and triggers formation of new structures of the cell skeleton (yellow) that allow the cell to move. Courtesy of PNAS.
“We were interested in the idea that you could activate receptors on a single area of a cell’s exterior,” Gautam said. “It’s what happens naturally when an immune cell senses something amiss in its environment and then migrates toward that potential trouble, perhaps a bacterial infection or inflammation.”

Several different opsins were introduced into immune cells. After demonstrating that those cells had an affinity for light, Gautam and postdoctoral research associate Dr. Ajith Karunarathne performed the same experiment with nerve cells, with equal success. The idea is to “trick” the cells into thinking that the opsin is a normal receptor protein.

The light-sensing opsin that they sneaked into immune and nerve cells belongs to a family of receptors called G protein-coupled receptors, which play a significant role in vision, smell, behavior and mood, regulation of the immune system, heart rate and the spread of some tumors.

Gautam’s team also made nerve cells grow branches, called neurites, by exposing the cells to light. The findings were published online in PNAS (doi: 10.1073/pnas.1220697110). The laboratory is now working with cardiac cells to test whether light signals can speed up or slow down the rate at which heart cells pulse.

“Eventually, we would like to introduce multiple light-sensing proteins into these cells,” Karunarathne said. “The idea would be to use two different wavelengths of light. That way, when you shine one light, for example, it could signal the first light-sensing protein to make the heart beat faster. Then a different wavelength of light could be used to slow down the heart rate.”

In future studies, the investigators plan to use the same kind of strategy to learn whether light can influence insulin secretion and the regeneration of nerve cells. The approach also is being used to study signaling circuitry in cells to see how networks of molecular pathways control cell behavior.

“This strategy can be valuable,” Gautam said. “We can control migration of cells, which is important not only to the immune system, but also during embryonic development, to ensure that cells that make the heart, liver and other organs go to the right place. It’s also key in cancer metastasis, when a tumor releases cells that migrate to other parts of the body. We are excited by the many possibilities.” The findings – supported by the National Institute of General Medical Sciences and the National Institutes of Health – appeared in PNAS (doi: 10.1073/pnas.1220755110).